Biomarker Discovery in Rare Malignancies: Development of a miRNA Signature for RDEB-cSCC.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37444397", "kind": "science-record", "revision": 3, "content_hash": "sha256:52de8416fab358e3cf6bac3e511b5a7a11d0f48a276e86bdd6bd84538bded4a1", "created_at": "2026-11-01T19:02:13Z", "updated_at": "2026-11-01T22:09:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Biomarker Discovery in Rare Malignancies: Development of a miRNA Signature for RDEB-cSCC.", "doi": "10.3390/cancers15133286", "pmid": "37444397", "authors": ["Roland Zauner", "Monika Wimmer", "Sabine Atzmueller", "Johannes Proell", "Norbert Niklas", "Michael Ablinger", "Manuela Reisenberger", "Thomas Lettner", "Julia Illmer", "Sonja Dorfer", "Ulrich Koller", "Christina Guttmann-Gruber", "Josefina Piñón Hofbauer", "Johann W Bauer", "Verena Wally"], "journal": "Cancers", "year": 2023, "abstract": "Machine learning has been proven to be a powerful tool in the identification of diagnostic tumor biomarkers but is often impeded in rare cancers due to small patient numbers. In patients suffering from recessive dystrophic epidermolysis bullosa (RDEB), early-in-life development of particularly aggressive cutaneous squamous-cell carcinomas (cSCCs) represents a major threat and timely detection is crucial to facilitate prompt tumor excision. As miRNAs have been shown to hold great potential as liquid biopsy markers, we characterized miRNA signatures derived from cultured primary cells specific for the potential detection of tumors in RDEB patients. To address the limitation in RDEB-sample accessibility, we analyzed the similarity of RDEB miRNA profiles with other tumor entities derived from the Cancer Genome Atlas (TCGA) repository. Due to the similarity in miRNA expression with RDEB-SCC, we used HN-SCC data to train a tumor prediction model. Three models with varying complexity using 33, 10 and 3 miRNAs were derived from the elastic net logistic regression model. The predictive performance of all three models was determined on an independent HN-SCC test dataset (AUC-ROC: 100%, 83% and 96%), as well as on cell-based RDEB miRNA-Seq data (AUC-ROC: 100%, 100% and 91%). In addition, the ability of the models to predict tumor samples based on RDEB exosomes (AUC-ROC: 100%, 93% and 100%) demonstrated the potential feasibility in a clinical setting. Our results support the feasibility of this approach to identify a diagnostic miRNA signature, by exploiting publicly available data and will lay the base for an improvement of early RDEB-SCC detection.", "claims": [{"id": "claim-method", "statement": "Normalized (DESeq2) miRNA-Seq count data were z-transformed before training a binomial generalized linear elastic net model (glmnet package).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37444397", "locator": "sections[12] \"2.10. Elastic Net Model Training and Performance Evaluation\" paragraph 2", "quote": "Normalized (DESeq2) miRNA-Seq count data were z-transformed before training a binomial generalized linear elastic net model (glmnet package)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are available upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37444397", "locator": "sections[33] \"Data Availability Statement\" paragraph 2", "quote": "The data that support the findings of this study are available upon request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Three elastic net logistic regression models using 33, 10 and 3 miRNAs discriminated between tumor and healthy cells, achieving AUC-ROC values of 100%, 83% and 96% on an independent HN-SCC test dataset, 100%, 100% and 91% on cell-based RDEB miRNA-Seq data, and 100%, 93% and 100% on RDEB exosomes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37444397", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Three models with varying complexity using 33, 10 and 3 miRNAs were derived from the elastic net logistic regression model. The predictive performance of all three models was determined on an independent HN-SCC test dataset (AUC-ROC: 100%, 83% and 96%), as well as on cell-based RDEB miRNA-Seq data (AUC-ROC: 100%, 100% and 91%). In addition, the ability of the models to predict tumor samples based on RDEB exosomes (AUC-ROC: 100%, 93% and 100%) demonstrated the potential feasibility in a clinical setting."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Three elastic net logistic regression models using 33, 10 and 3 miRNAs discriminated between tumor and healthy cells, achieving AUC-ROC values of 100%, 83% and 96% on an independent HN-SCC test dataset, 100%, 100% and 91% on cell-based RDEB miRNA-Seq data, and 100%, 93% and 100% on RDEB exosomes.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37444397"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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Figure S3: Mature arm selection for TaqMan qPCR validation of up-regulated SIG-10 miRNAs. Fi", ". Figure S4: Mature arm selection for TaqMan qPCR validation of down-regulated SIG-10 miRNAs.", "of down-regulated SIG-10 miRNAs. Figure S5: qPCR validation of SIG-10 miRNAs in RDEB tumor ce"], "order_basis": "paper_text_order:6247", "id": "assay:2"}, {"role": "analysis", "definition_id": "principal_component_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pca_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["PCA"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}